This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. SPECIFIC AIMS Primary Objective To compare the reduction in the rate of histologic fibrosis progression from Step 2 entry to study termination between subjects treated with PEG-IFN and untreated controls in subjects with HIV-1 and hepatitis C virus (HCV) coinfection who have failed to respond to 12 weeks of PEG-IFN plus ribavirin. Secondary Objectives [unreadable] To evaluate the quality of life associated with long-term PEG-IFN in coinfected subjects. [unreadable] To determine the impact of long-term PEG-IFN use on HCV viral evolution and host immunologic response. [unreadable] To investigate the role of noninvasive markers of fibrosis in predicting histologic response, including ALT, AST, bilirubin, albumin, and protein. [unreadable] To determine the effect of long-term PEG-IFN versus untreated controls on CD4+ T-cell counts and AIDS-defining illnesses. [unreadable] To determine the effect of long-term PEG-IFN therapy on metabolic parameters, including body weight, lipid profile, hyperglycemia, and insulin resistance. [unreadable] To assess the impact of treatment on HIV disease control. [unreadable] To determine the influence of host genetic polymorphisms on cytokine and fibrosis-related genes on baseline histology and on histologic progression of disease.